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- Title
The role of clonal progression leading to the development of therapy-related myeloid neoplasms.
- Authors
Guarnera, Luca; Pascale, Maria Rosaria; Hajrullaj, Hajro; Cristiano, Antonio; Mallegni, Flavia; Onorato, Angelo; Voso, Maria Teresa; Fabiani, Emiliano
- Abstract
Therapy-related myeloid neoplasms (t-MN) are characterized by aggressive features and a dismal prognosis. Recent evidence suggests a higher incidence of t-MN in individuals harboring clonal hematopoiesis of indeterminate potential (CHIP). In order to gain insight into CHIP-driven malignant progression, we gathered data from ten published reports with available detailed patient characteristics at the time of primary malignancy and t-MN development. Detailed clinical and molecular information on primary malignancy and t-MN were available for 109 patients: 43% harbored at least one somatic mutation at the time of the primary malignancy. TET2 and TP53 mutations showed an increasing variant allele frequency from CHIP to t-MN. ASXL1-associated CHIP significantly correlated with the emergence of TET2 and CEBPA mutations at t-MN, as well as U2AF1-driven CHIP with EZH2 mutation and both IDH2 and SRSF2-driven CHIP with FLT3 mutation. DNMT3A-driven CHIP correlated with a lower incidence of TP53 mutation at t-MN. In contrast, TP53-driven CHIP correlated with a complex karyotype and a lower tendency to acquire new mutations at t-MN. Patients with multiple myeloma as their first malignancy presented a significantly higher rate of TP53 mutations at t-MN. The progression from CHIP to t-MN shows different scenarios depending on the genes involved. A deeper knowledge of CHIP progression mechanisms will allow a more reliable definition of t-MN risk.
- Subjects
SOMATIC mutation; MULTIPLE myeloma; GENE frequency; HEMATOPOIESIS; KARYOTYPES
- Publication
Annals of Hematology, 2024, Vol 103, Issue 9, p3507
- ISSN
0939-5555
- Publication type
Article
- DOI
10.1007/s00277-024-05803-y